Recent developments in ambient desorption ionization techniques, such as desorption electrospray ionization (hereinafter, “DESI”) and direct analysis in real time (hereinafter, “DART”), have opened new routes for characterizing a wide range of compounds, such as proteins, explosives, polymers, pharmaceuticals and metabolites amenable to mass spectrometry, with little or no sample preparation. In addition, DESI techniques (such as that disclosed in U.S. Pat. No. 7,335,897, the disclosure of which is incorporated by reference herein) have been extended to biological imaging as well. The ionization mechanisms of both DESI and DART correlate to those of at least two other sample ionization techniques. For example, the DESI technique is a modification of the well-known electrospray ionization (hereinafter, “ESI”) method, whereas the DART technique is related to the well-known direct atmospheric pressure ionization (hereinafter, “DAPCI”) procedure. In the ESI-related DESI technique, analytes are desorbed from a sample surface. Desorption takes place mainly through momentum transfer from charged solvent droplets, although other processes also occur (e.g., volatilization, reactive ion/surface collisions, and charge transfer from even-electron ions). In contrast, DAPCI-related desorption techniques mainly desorb analytes by momentum transfer from uncharged droplets, with ionization taking place after desorption.
Despite the major breakthroughs of sample analysis provided by DESI and DART, both techniques have some limitations. The DART technique can be applied primarily to low-molecular-weight samples (i.e., samples having molecular weights of less than about 1 kiloDaltons (kDa)) and has a very limited dynamic range. The DESI technique, in contrast, can ionize samples having molecular weights as high as 66 kDa and has a high dynamic range of about 1000. However, DESI is a highly inefficient technique for generating ions from molecules of low polarity. Even polar molecules such as cholesterol and 1,4-hydroquinone are poorly ionized by DESI methods in positive mode. Further, DESI methods regularly produce protonated or sodiated molecular ions or fragments, complicating interpretation of mass spectrographs.